tbuckley/cabot-search huggingface dataset:
Abstract P6-07-01: Costs of breast cancer recurrence after initial treatment for high risk early breast cancer using SEER-Medicare linked data
Authors: Alexandra S. Vitko, Pamela A. Martin, Sheng Zhang, Adam F. Johnston, Robert L. Ohsfeldt, Shen Zheng, Astra M. Liepa
Journal: Cancer Research (2023)

Abstract Background: Despite the good prognosis with treatment for most patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) early breast cancer (EBC), ~ 20–30% of patients experience locoregional or distant disease recurrence. To assist in value assessments of novel therapies in the adjuvant setting, this study aimed to determine the costs of treated breast cancer recurrence following treated EBC. Methods: This retrospective study analyzed linked patient data from the US Surveillance Epidemiology and End Results (SEER) registry (2010-2014) and Medicare claims (2009 to 2019, which included data from Part A, B, and Prescription Drug Events [Part D]). Data were analyzed for patients aged ≥65 years with HR+, HER2-, node-positive EBC at high risk of recurrence (consistent with monarchE trial high risk criteria). Treated recurrences were defined based on treatment events/procedure codes, including surgery, radiation and systemic therapy, after a 90-day gap following the last treatment for initial EBC. Recurrences were classified based on Medicare claim diagnosis codes or SEER registry data. Extra cost was defined as cost attributable to treated recurrence. Cumulative extra costs were estimated by calculating cost differences between patients with treated vs non/untreated recurrence. Cumulative extra costs were analyzed over the first 6 years following first treated recurrence, a duration which ensured adequate sample size. Costs were inflated to 2021-US$. Results: We identified 3081 eligible patients (mean age at diagnosis 74.5±7.1 years, 97.4% female, 87.8% White). We identified 964 patients with treated recurrence (distant=432, locoregional=128, contralateral=9, unclassified=347) and 2117 patients with non/untreated recurrence. Six-year cumulative extra costs were higher for patients with distant recurrences ($168,656) than for patients with locoregional recurrences ($96,465) (Table 1). Conclusions: Cost of recurrence in patients with high risk EBC is considerable, particularly in patients with distant recurrences. Most patients who recurred in this population experienced distant recurrence. Delaying or preventing recurrence may reduce long term costs in these high risk EBC patients. Table 1. Mean cumulative extra costs attributable to treated recurrence. Citation Format: Alexandra S. Vitko, Pamela A. Martin, Sheng Zhang, Adam F. Johnston, Robert L. Ohsfeldt, Shen Zheng, Astra M. Liepa. Costs of breast cancer recurrence after initial treatment for high risk early breast cancer using SEER-Medicare linked data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-07-01.
Abstract P5-13-05: Profiling of APOBEC3 dysregulation in breast cancer
Authors: Hamid Hamidi, Azad Khosh, Hamzeh Rahimi, Diako Ebrahimi
Journal: Cancer Research (2023)

Abstract DNA of many breast tumors is barraged by C-to-T/G mutations within TCW (W:T,A). These mutations are attributed to the aberrant expression and activity of APOBEC3 enzymes. They have been shown to account for many driver mutations in genes such as PIK3CA, ERBB2, and PPP2R1A, however their precise source and also their roles in tumor development, evolution, and patient survival are debated. Currently, quantification of APOBEC3 expression changes in tumor cells is confounded by the ubiquitous expression of these enzymes in immune infiltrating cells. In this study, we used a novel quantitative biology approach to determine the expression profiles of APOBEC3 enzymes in breast tumor and tumor microenvironment cells from &amp;gt;1,000 patients. We combined diverse datasets including tumor/matched normal RNAseqs, tumor somatic mutations, cell line RNAseqs and mutations, estimates of tumor purities and immune cell compositions, and expression of purified cell populations to show that in breast cancer there is only a single APOBEC3 dysregulation process. This process is subtype-independent and is represented by APOBEC3B upregulation and and extreme APOBEC3C downregulation. Compared to all other tumor types, breast tumors are affected the most by this process. Citation Format: Hamid Hamidi, Azad Khosh, Hamzeh Rahimi, Diako Ebrahimi. Profiling of APOBEC3 dysregulation in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-13-05.
Abstract P4-05-05: The Psycho-Social Factors Impacting Black Women Breast Cancer Survivors
Authors: Virginia Leach
Journal: Cancer Research (2023)

Abstract Background: Breast Cancer (BC) mortality rates disproportionately affect African American (AA) women over any other racial or ethnic group in the United States. However, questions about how AA women who survive the disease navigate psychosocial factors such as body image, self-esteem, stigma and shame, thoughts and fears surrounding fertility, and romantic relationships remain unanswered. This study’s primary research question is, "How do AA women BC survivors create a new normal post-breast cancer while figuring out their own identity?" Methods: This qualitative study aims to address the psychosocial factors experienced by 20 AA women BC survivors in the U.S. The 20 women were recruited to participate in the IRB-approved study (University of Illinois at Urbana-Champaign) through the Tigerlily Foundation, a non-profit breast cancer advocacy organization. The total duration of the study lasted a maximum of 1 hour and 45 minutes with participants answering one pre-interview questionnaire for demographic purposes and one interview with a member of the research team. Results: Preliminary results from the data conclude that AA women BC survivors, and potentially all cancer survivors, mirror individuals in the postpartum phase. Being postpartum is not inherently harmful; however, if one begins to experience symptoms of depression, loss of appetite, irritability, and insomnia for an extended period, there is a high possibility they are experiencing Postpartum Depression (PPD). BC survivors experience numerous changes that can drastically impact their quality of life. AA women BC survivors struggle immensely with body image and self-confidence issues after experiencing breast cancer, various surgeries, and treatments. Conclusion: If BC survivors, particularly AA women BC survivors experiencing systemic and institutional racism, are treated with the same care postpartum individuals are given, there can be a shift in how oncologists work with BC survivors. Creating more personalized survivorship care plans between patients, oncologists, and hospital-based social workers can improve psychosocial factors experienced by AA women BC survivors. Citation Format: Virginia Leach. The Psycho-Social Factors Impacting Black Women Breast Cancer Survivors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-05-05.
Abstract P6-05-07: Oncologic outcomes of pregnancy after surgical treatment of breast cancer 35 years old or under
Authors: Ji Hye Kim, Sang Uk Woo, Jae Bok Lee, Woo Young Kim, Jai Hyun Chung, Yong Yeup Kim
Journal: Cancer Research (2023)

Abstract Purpose: Recent advances in the treatment of breast cancer has led to the improvement of breast cancer patient’s survival. With prolonged survival of these patients, pregnancy became an important issue, especially in those of young cancer patients aged 35 or under. Increased hormone levels during pregnancy, however, raises concerns of elevating the risk of cancer recurrence. The aim of this study was to validate the notion of increased risk associated with pregnancy after breast cancer treatment in young patients. Methods: From January 2009 to December 2020, newly diagnosed breast cancer patients of 35 years old or under who underwent curative surgery in Korea University Guro Hospital were enrolled in this study. Patients were categorized into 3 groups: nulliparous, pregnancy prior to treatment of breast cancer, and patients with pregnancy after breast cancer treatment. Their overall survival and disease-free survival were evaluated. Results: A total of 126 patients was enrolled in this study. Seventeen patients (13.4%) conceived and successfully delivered. The mean age of enrolled patients was 32.0 years old (± 3.1), and the mean follow up period after surgery was 56.8 months (± 34.2). There was no significant difference in overall survival (p=0.490) and disease-free survival (p=0.740) among different groups. Among 22 patients with re-diagnosis of breast cancer, 2 of them (9%) had breast cancer on their contralateral breast. Conclusion: In young patients, pregnancy after treatment for breast cancer did not affect their overall survival or disease-free survival as compared to nullipara or previously delivered groups. Therefore, pregnancy counseling should not be prevented in young breast cancer patients of 35 years old or under. Citation Format: Ji Hye Kim, Sang Uk Woo, Jae Bok Lee, Woo Young Kim, Jai Hyun Chung, Yong Yeup Kim. Oncologic outcomes of pregnancy after surgical treatment of breast cancer 35 years old or under [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-07.
Abstract P4-08-25: Unravelling the role of human endogenous retrovirus K (HERV-K) in inducible nitric oxide synthase (iNOS) mediated triple negative breast cancer progression
Authors: Dibyangana Bhattacharyya, Eoin Dervan, Sharon Glynn, Grace Callagy
Journal: Cancer Research (2023)

Abstract Human endogenous retrovirus K (HERV-K) belongs to a family of endogenous retroviruses that are present in our genome with similarities to present day exogenous retroviruses. This virus can express several proteins but our knowledge of HERV-K expression in human cancers is mainly limited to the envelope (Env) protein. Elevated HERV-K env protein expression has been shown in breast cancer both in in vitro and in vivo studies. This project aimed to decipher mechanisms of HERV-K induction in triple negative breast cancer (TNBC), and the impact of HERV-K targeting shRNA mediated knockdown on TNBC characteristics including cell migration, invasion and proliferative capacity in 2D and 3D cell culture models. Our results show that a role for inducible nitric oxide synthase (iNOS) in the induction of HERV-K in TNBC cell lines. RNA seq and bioinformatics analysis was performed to identify key molecular processes regulated by HERV-K and nitric oxide (NO) in MDA-MB-231 TNBC cells. Reduced rates of migration, invasion and proliferation in HERV-K knockdowns points towards the essential role of HERV-K in tumorigenesis and metastasis. HERV-K knockdown also modulated key gene expression signatures traditionally associated with the basal and mesenchymal phenotypes in breast cancer, cellular senescence and MHC class gene regulation. The co-expression of iNOS and HERV-K was assessed in over 150 TNBC cases and the association with patient outcomes assessed. Taken together, our findings indicate that NO and HERV-K may be a useful molecular target for the treatment of TNBC. Citation Format: Dibyangana Bhattacharyya, Eoin Dervan, Sharon Glynn, Grace Callagy. Unravelling the role of human endogenous retrovirus K (HERV-K) in inducible nitric oxide synthase (iNOS) mediated triple negative breast cancer progression [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-25.
Abstract P4-02-08: Towards Precision Radiation Oncology: Endocrine Therapy Resistance as a Biomarker for Radiation Resistance in ER-Positive Breast Cancer
Authors: SM Nashir Udden, Asal Rahimi, Dong W. Nathan Kim, Prasanna Alluri
Journal: Cancer Research (2023)

Abstract Pre-operative endocrine therapy use in post-menopausal women with localized, ER-positive breast cancer affords comparable rates of response and breast preservation, but lower toxicity relative to chemotherapy. Pre-operative endocrine therapy exerts selective pressure on cancer cells and promote evolution and/or enrichment of pathogenic alternations such as ESR1 mutations and other cellular adaptations. How such endocrine therapy-induced adaptations alter response to radiation therapy remains poorly defined. In this study, we show that diverse mechanisms that confer endocrine therapy resistance also drive radiation resistance by reprogramming of DNA repair pathways. We also show that BRD4, a member of bromodomain and extraterminal domain (BET) family of proteins, mediates such DNA repair reprogramming. BRD4 also plays a key role in trascriptional reprogramming in ER-positive breast cancer cells that confers endocrine therapy resistance. Thus, OTX015, a BET inhibitor with a favorable safety profile in early stage clinical trials, reverses both endocrine therapy resistance and radiation resistance in ER-positive breast cancer cells and tumors. Our findings are also consistent with reports that tamoxifen-resistant breast cancer cells are resistant to DNA damaging chemotherapeutic agents such as adriamycin and cisplatin. Overall, our findings suggest that endocrine therapy resistance in the pre-operative setting serves as a biomarker for reduced response to adjuvant radiation therapy, and that pharmacological BET inhibition reverses radiation resistance in such patients. The increasing use of “window of opportunity” studies to assess response to endocrine therapy in the pre-operative setting will further facilitate personalization of radiation treatments in these patients based on their response to endocrine therapy. Thus, we provides a therapeutic rationale for personalization of radiation treatments in breast cancer patients based on their response to endocrine therapy. We also provide a molecularly targeted approach for reversing radiation resistance in such patients. Thus, our study provides a framework for advancing Precision Radiation Oncology in breast cancer patients. Citation Format: SM Nashir Udden, Asal Rahimi, Dong W. Nathan Kim, Prasanna Alluri. Towards Precision Radiation Oncology: Endocrine Therapy Resistance as a Biomarker for Radiation Resistance in ER-Positive Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-08.
Abstract P6-05-33: Distress Reduction and Physical Activity Enhancement by Mobile Support Group in Breast Cancer Survivors: a randomized controlled study
Authors: Il-Yong Chung, Miyeon Jung, Sae Byul Lee, Jong Won Lee, Sei Hyun Ahn, Haekwon Chung
Journal: Cancer Research (2023)

Abstract Purpose Improving physical activity (PA) and reducing mental distress are important issues in the treatment of cancer survivors. This study aimed to investigate the effect of a mobile app-based community on enhancing PA and decreasing distress in breast cancer survivors. Methods We conducted a single-center, prospective, non-blinded, randomized controlled study. Subjects who got breast cancer surgery were allocated to a control group or a app-based community group (intervention) where members were able to share their daily physical activities. Daily walk steps and weekly distress scores using app-based Distress Thermometer (DT) questionnaires were collected from participants for 24 weeks. To examine the differences in levels of distress and weekly step counts for 6 months, we used a t-test method and multivariable regression modeling. Results From Jan 2019 to Apr 2020, a total of 202 participants were enrolled in this study. The intervention group showed a significant increase in weekly steps by 4,496 for 6 months (p &amp;lt; 0.001). The participants in the intervention group showed a significantly lower rate of above mild distress (DT≥3, beta[B] = -0.731, p &amp;lt; 0.001) and above moderate distress (DT≥5, B = -0.558, p &amp;lt; 0.001) compared to those in the control group for 6 months. Conclusions The mobile app-based community is an effective and less resource-intensive tool to increase PA and decrease distress in breast cancer survivors. Citation Format: Il-Yong Chung, Miyeon Jung, Sae Byul Lee, Jong Won Lee, Sei Hyun Ahn, Haekwon Chung. Distress Reduction and Physical Activity Enhancement by Mobile Support Group in Breast Cancer Survivors: a randomized controlled study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-33.
Abstract P4-08-24: Palmitoylation of Flotillin-1 contributes to Breast Cancer Metastasis
Authors: Bryan McClellan
Journal: Cancer Research (2023)

Abstract BACKGROUND Breast Cancer metastasis results in the majority of cancer-related mortality. Flotillin-1 is overexpressed in numerous solid tumors and has been demonstrated to contribute to invasion and metastasis in breast cancer. Though its expression alone has been associated with metastasis, there has yet to be any investigation as to how certain post-translational modifications can affect its metastatic capabilities. Flotillin-1 is modified through palmitoylation, a post-translational modification essential for protein stability, processing, and localization. By generating a palmitoylation defective mutant of flotillin-1, we have demonstrated that flotillin-1 palmitoylation contributes to its stability and metastatic capabilities in both 3D and in vivo models of invasion and metastasis. MATERIALS AND METHODS Flotillin-1 wild type or palmitoylation defective C-34-A mutants were expressed in stable flotillin-1 knockdown MDA-MB-231 and SUM-159 triple negative breast cancer cells. These cells were subjected to 2D invasion chambers and 3D collagen invasion assays. Further, both wild type and C34A expressing cells were used for experimental lung metastases in mice by tail vein injection. 2-bromopalmtiate (50µM) was used as a chemical palmitoylation inhibitor and MG-132 (10µM) for proteasomal inhibition. RESULTS Invasion in stable knockdown cells was restored by re-expression of flotillin-1, but not by follitillin-1 C34A. We further observed a significant decrease in lung metastasis in flotillin-1 C34A cells compared to wild type flotillin-1. Flotillin-1 C34A expression led to a significant decrease in protein stability, which was restored by MG-132. CONCLUSION Flotillin-1 palmitoylation contributes to its stability and subsequent metastatic capabilities in breast cancer cells and experimental metastasis models. Thus, flotillin-1 palmitoylation could be a promising target for breast cancer metastasis. Citation Format: Bryan McClellan. Palmitoylation of Flotillin-1 contributes to Breast Cancer Metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-24.
Abstract P1-11-03: VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers
Authors: Yikyung Ko, Jihye yoo, Hong-ryul Jung, Hyerim Lim, YeongDeok Lee, Se Hyuk Kim, Dong Guk Shin, Serin Cho, Myung hoe Heo, Haelee Kim, Ha Yeon Cho, Ah Reum Han, Eunhwa Ko, Hwan Geun Choi, Deakwon Kim, Sunghwan Kim
Journal: Cancer Research (2023)

Abstract The brain is a common target organ for breast cancer metastasis, and the risk of brain metastasis is usually high for patients with HER2-positive breast cancer. While T-DXd showed positive results in HER2-positive breast cancer brain metastasis (BCBM), its activity and blood-brain barrier (BBB) permeability in active BCBM need to be further validated (TUXEDO-1 included 15 patients with active brain metastasis). Tucatinib plus Trastuzumab and Capecitabine triplet showed efficacy in patients with brain metastasis, but Tucatinib alone has poor BBB penetration. There is still an unmet medical need for active HER2-positive BCBM. VRN101099 is a highly selective kinase inhibitor of HER2 (Eurofins scanMAX Kinase Profiling, S-score (35) of 0.01). VRN101099 has single- to double-digit nanomolar (IC50) cellular potency in HER2-dependent cancer cells, and Ba/F3 cells expressing HER2 wild type or mutations with selectivity over wildtype EGFR. VRN101099 inhibited proliferation of BT474 with 3.6 nM IC50 but HaCaT with 829.2 nM IC50. VRN101099 binds HER2 kinase by forming a covalent bond to the Cys805 and its irreversible inhibition resulted in a longer target resident time than Tucatinib, confirmed by in vitro washout experiments. Robust in vivo activity of VRN101099 was observed in HER2-positive BT474 xenograft models. Moreover, once daily oral administration of VRN101099 significantly regressed intracranial BT474 tumor, demonstrating greater efficacy than twice daily oral administration of Tucatinib. These results were well explained by the superior brain to plasma exposure of VRN101099 to Tucatinib. Also, VRN101099 showed high exposure in the target organ, the fat pad, which potentiated better clinical translation. These anti-tumor efficacies are correlated with pharmacodynamic responses, as confirmed by decreased HER2, AKT, and ERK phosphorylation. In summary, VRN101099 is a brain penetrant, orally bioavailable, irreversible, and highly selective inhibitor of HER2 with therapeutic potential in HER2-positive BCBM. These data support the clinical development of VRN101099 in HER2-driven cancers. Citation Format: Yikyung Ko, Jihye yoo, Hong-ryul Jung, Hyerim Lim, YeongDeok Lee, Se Hyuk Kim, Dong Guk Shin, Serin Cho, Myung hoe Heo, Haelee Kim, Ha Yeon Cho, Ah Reum Han, Eunhwa Ko, Hwan Geun Choi, Deakwon Kim, Sunghwan Kim. VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-03.